Stratum corneum pharmaco­kinetics of the anti-fungal drug, terbinafine, in a novel topical formulation, for single-dose application in dermatophytoses

Abstract

The SC pharmacokinetic profile of terbinafine 1% FFS indicates that this novel formulation is efficient in delivering high amounts of terbinafine to the skin for a prolonged time and supports its use in the treatment of dermatophytoses with a single application.

Fungicidal Activity Plus Reservoir Effect Allow Short Treatment Courses with Terbinafine in Tinea pedis

“…The authors concluded that the increasing efficacy of terbinafine after the end of the treatment period can be accounted for not only by the fungicidal effect but also in particular by its favorable pharmacokinetic characteristics of substantial and rapid penetration into the stra-tum corneum and remanence in the tissue for a long time after discontinuation of treatment. This is particularly evident with the new terbinafine formulation, where the cure rates continue to increase for up to 6 weeks after a single application [36] .…”

“…Similarly, single-application terbinafine 1% FFS has also shown a low incidence of side effects [34,36] . Thus, terbinafine is as effective and safe as azoles but is superior with regards to effectiveness based on its remarkably short treatment duration (i.e.…”

“…Based on several studies conducted in humans [36,[38][39][40][41] and animals [42,43] , it has been noted that terbinafine accumulates in the skin after topical or oral application and persists at high concentrations up to several weeks after discontinuation of drug application. Being highly lipophilic, terbinafine attaches to keratinocytes and thereby remains in the stratum corneum for a long time [44] .…”

“…Terbinafine also accumulates in the nails, hair, dermis/epidermis and in subcutaneous fat tissues [39,40] after oral treatment. Long-term retention in the skin is also evident after topical application of terbinafine, while the permeation into the systemic circulation is minimal as evidenced from pharmacokinetic studies in human volunteers and patients with tinea pedis [36,41,45,46] . Twenty healthy volunteers were randomized to receive terbinafine 1% cream applied to the upper back as a single dose, or once daily for 3, 5 or 7 consecutive days [41] .…”

“…The high concentration gradient results in pronounced terbinafine skin penetration, which is further facilitated by the alcohol [49][50][51] . Moreover, the adhesion of the polymer matrix inhibits the removal of terbinafine from the skin surface and thus induces an ongoing absorption process for an additional few days -in the absence of early skin washing within the first 24 h after application [36] .…”